Fused thiazolidene derivatives of formula (I), particularly thiazolo-pyridinylidene compounds have demonstrated activity as Cannabinoid (CB) Receptor ligands, more particularly as selective CB2 receptor ligands. Such ligands provide useful compounds for pharmaceutical products. For example, CB2 receptor ligands can be used for treatment of disorders or conditions related pain such as, but not limited to, chronic pain, neuropathic pain, nociceptive pain, osteoarthritic pain, inflammatory pain, cancer pain, lower back pain, post operative pain, and eye pain; inflammatory disorders, immune disorders, neurological disorders, cancers of the immune system, respiratory disorders, obesity, diabetes, cardiovascular disorders, or for providing neuroprotection.
Previous processes for preparing compounds of formula (I) generally involved a three-step reaction:
(a) coupling of thiazolopyridine-2-amine with a substituted 2-fluorobenzoic acid;
(b) alkylation of the resulting benzamide from step (a) with alkyl halide in the presence of potassium carbonate, under biphasic reaction conditions; and
(c) displacing the fluoride with an appropriate un-protected diol.
While these processes were able to provide analogs of sufficient quantity of compounds of formula (I), and particularly the thiazolo-pyridinylidene analogs for SAR (structural activity relationship) study, the overall low yields of the procedures do not have utility for large scale synthesis. Thus it would be beneficial to provide efficient processes for preparing such compounds of increasing reaction product yield.